Ch7 chromosome mutation variation in number and arrangement
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Ch7. Chromosome Mutation Variation in Number and Arrangement. Although most members of diploid species normally contain precisely two haploid chromosome sets, many known cases vary from this pattern.

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Ch7. Chromosome Mutation Variation in Number and Arrangement

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Ch7. Chromosome MutationVariation in Number and Arrangement

Although most members of diploid species normally contain precisely two haploid chromosome sets, many known cases vary from this pattern.

Modifications include a change in the total number of chromosomes, and changes of chromosomal structures, the deletion or duplication of genes or segments of a chromosome, and rearrangements of the genetic material either within or among chromosomes.

  • Taken together, such changes are called chromosome mutations or chromosome aberrations, to distinguish them from gene mutations.

  • Because, according to Mendelian laws, the chromosome is the unit of genetic transmission, chromosome aberrations are passed on to offspring in a predictable manner, resulting in many unique genetic outcomes.

  • 7.1 Variation in Chromosome Number :An Overview

  • 7.2 Nondisjunction :The origin of Aneupoidy

  • 7.3 Monosomy

  • 7.4 Trisomy

  • 7.5 Polypoidy and its Origin

  • 7.6 Variation in Chromosome Structure and Arrangement: An Overview

  • 7.7 Deletion

  • 7.8 Duplication

  • 7.9 Inversion

  • 7.10 Translocation

  • 7.11 Fragile Sites In Humans

A change in Genetic material---mutation

  • Numbers of chromosomes

    Euploidy(): monoploidy and polyploidy

    polyploidy :Autopolyploidy() Allopolyploids()

    Aneuploidy(): loss 2n- 1 or more and add 2n+1 or more of the whole set of chromosomes

  • Rearrangement (Structural alterations) of chromosomes





1.Variation in Chromosome Number:Overview

  • Changes in chromosome number can occur by the addition of or the loss of all or part of an entire set of chromosomes

  • Aneuploidy: the loss or the gain of one or more of normal set chromosomes. Each of these conditions is a variation on the normal diploid number of chromosomes.

  • EuploidyChanges by an entire set of chromosomes ,Euploidy - an entire set of chromosomes is duplicated once or several times


Species A


Species B


Species C

























  • In addition to these conditions, more than one pair of homologous chromosomes may be involved. For example,

  • a double monosomic is missing one chromosome from each of two pair of homologous chromosome (designated 2N-1-1),

  • a double tetrasomic contains an extra pair of two pairs of homologous chromosomes (2N+2+2).

  • telocentrics which are chromosomes that have a terminal centromere. These structures represent chromosomes that are missing the genetic material beyond that centromere. (Stocks containing these types of chromosomes are called

  • monotelosomics or monotelos (for short.

  • isochromosome which is a chromosome that contains the same genetic material on both arms.

2.Nondisjunction :The origin of Aneuploidy

  • The development of aneuploids is not well understood, but they may have arisen by a process called nondisjunction. Nondisjunction occurs when paired chromosomes do not separate either during meiosis I or meiosis II. The direct result of this event is that gametes develop that have too few or too many chromosomes. If this occurs during meiosis I normal gametes are not developed, and if it occurs during meiosis II half of the gametes will be normal and the other half will be abnormal.

  • Non-disjunction can also occur during mitosis and the result is an individual that expresses chromosomal mosaicism().

  • If this occurs during the early stages of cell divisions different portions of the body which descended from the different altered cells will beformed.

  • (See figure 19.20.) Many sex chromosome mosaics have been detected for example X/XX, X/XY, XX/XY and XXX/XXXXY. Mild to severe phenotypic symptoms have been associated with these mosaics

7.3 Monosomy

  • We turn now to a consideration of variations in the number of autosomes and the genetic consequence of such changes. The most common examples of aneuploidy where an organism has a chromosome number other than an exact multiple of the haploid set, are cases in which a single chromosome is either added to, or lost from, a normal diploid set. The loss of one chromosome produces a 2n - 1 complement and is called monosomy.

  • Although monosomy for the X chromosome occurs in humans, as we have seen in 45,X Turner syndrome, monosomy for any of the autosomes is not usually tolerated in human or other animals.

  • Monosomy

  • 2n=4221

  • 2n-II2121

  • ,2n-Inn-1

  • ,

  • (2)n-1 n

    (3)2n-II 2n-1

  • The failure of monosomic individuals to survive in many animal species is at first quite puzzling, since at least a single copy of every gene is present in the remaining homolog.

  • However, if just one of those genes is represented by a lethal allele, the unpaired chromosome condition leads to the death of the organism.

  • This occurs because monosomy unmasks recessive lethals that are tolerated in heterozygotes carrying the corresponding wild-type alleles.

  • Aneuploidy is better tolerated in the plant kingdom.

  • Monosomy for autosomal chromosomes has been observed in maize, tobacco, the evening primrose Oenoihera, and the Jimson weed Datura, among other plants.

  • Nevertheless, such monosomic plants are usually less viable than their diploid derivatives.

  • Haploid pollen grains, which undergo extensive development before participating in fertilization, are particularly sensitive to the lack of one chromosome and are seldom viable.

Cri-du-Chat Syndrome

In humans, autosomal monosomy has not been reported beyond birth. There are, however, examples of survivors where only part of one chromosome is lost. These cases are sometimes referred to as segmental deletions.

One such case was first reported by Jerome LeJeune in 1963 when he described the clinical symptoms of the cri-du-chat (cry of the cat) syndrome. This syndrome is associated with the loss of part of the short arm of chromosome 5 (Figure 7-2). of

Thus, the genetic constitution may be designated as 46,5p-, meaning that such an individual has all 46 chromosomes but that some

7.4 Trisomy

  • n+1n

  • n+1nIn+150%n+1n+1

  • 5111

Genetics of Aneuploids in fruit fly

  • Monosomics and trisomics are usually inviable in Drosophila. The exception are those aneuploids involving chromosome IV. Therefore the effects of aneuploidy on inheritance has been investigated using stocks with altered chromosome IV.

  • haplo-IV (monosomic for chromosome IV; 2n-1);

  • diplo-IV (normal; 2n) and

  • triplo- IV (trisomic for chromosome IV; 2n+1). Located on chromosome IV is the gene for eyeless (ey) that is recessive to normal eye. The following crosses illustrate several genetic principles of aneuploids. The first is a cross between a diplo-IV eyeless female (ey ey) and a haplo-IV normal eye male (ey+).

A1A2a 3 (A1A2 a3 A1a3 A2 ) X 2 (a2A1 A2 ) x 2


P a/a x +/+/+

F1 a/+/+ a/a

2/6 a/+ 2/6 + 1/6 +/+ 1/6 a

5 1

eyeless female (ey ey) and a haplo-IV normal eye male (ey+).

PATAU syndrome = trisomy 13

- facial defects, polydactyly, heart defects, die within a few months of birth

EDWARDS syndrome = trisomy 18

- small + muliple defects, usually die in first year of life

DOWN syndrome = trisomy 21

DOWN syndrome = trisomy 21


The karyotype and phenotypic depiction of an infantwith Patau syndrome, where three members of the D-group chromosome 13 are present, creating the 47,13+ condition.

FIGURE 74 Incidence of Down syndrome births contrasted with maternal age.

7.5 Polyploidy and Its OriginsEuploidy:

  • 19Oenothera lamarckiana1901O,

  • 19071909282n=28) 2n=14)

  • The term polyploidy describes instances in which more than two multiples of the haploid chromosome set are found. The naming of polyploids is based on the number of sets of chromosomes found:

  • A triploid has 3n chromosomes;

  • a tetraploid has 4n;

  • a pentaploid, 5n; and so forth.

  • Several general statements can be made about polyploidy. This condition is relatively infrequent in many animal species, but is well known in lizards, amphibians, and fish.

  • It is much more common in plant species.

  • Odd numbers of chromosome sets are not usually maintained reliably from generation to generation, because a polyploid organism with an uneven number of homologs often does not produce genetically balanced gametes.

  • For this reason, triploids, pentaploids, and so on, are not usually found in plant species that depend solely on sexual reproduction for propagation.

  • Polyploidy originates in two ways:

  • (1) The addition of one or more extra sets of chromosomes, identical to the normal haploid complement of the same species, resulting in autopolyploidy; and

  • (2) the combination of chromosome sets from different species occurring as a consequence of hybridization, resulting in allopolyploidy (from the Greek word allo, meaning other or different). The distinction between auto- and allopolyploidy is based on the genetic origin of the extra chromosome sets, as shown in Figure 7-6.

  • Euploidy in Animals

  • A genome that contains three or more full copies of the haploid chromosome number are polyploid. As a general rule polyploids can be tolerated in plants, but are rarely found in animals. One reason is that the sex balance is important in animals and variation from the diploid number results in sterility.

  • Those few animals, such as brine shrimp, that avoid the hazards of polyploidy, utilize parthenogenesis, the development of the an individual from an egg without fertilization, to initiate embryo development.

  • Euploidy in plants

  • Before we discuss polyploidy in plants in detail, first a distinction must be made between the two major classes of polyploids, autopolyploids and allopolyploids.

  • The following definitions will rely on these chromosomal descriptions. Two species will be considered, A and B. The chromosomal compositions of one species is: A = a1 + a2 + a3 . . . an

  • where a1, a2, etc. represent individual chromosomes and n is the haploid chromosome number.

  • The chromosomal composition of the second species will be:

  • B = b1 + b2 + b3 . . . bn

  • Autopolyploid - an individual that has an additional set of chromosomes that are identical to parental species;

  • an autotriploid would have the chromosomal composition of AAA and an autotetraploid would be AAAA; both of these are in comparison to the diploid with the chromosomal composition of AA

  • An autotriploid could occur if a normal gamete (n) unites with a gamete that has not undergone a reduction and is thus 2n. The zygote would be 3n.

  • Triploids could also be produced by mating a diploid (gametes = n) with a tetraploid (gametes = 2n) to produce an individual that is 3n. The difficulty arises when autotriploids try to mate because unbalanced gametes are produced because of pairing problems with the additional chromosome set. Thus, these are invariably sterile.

  • Allopolyploid - an individual that has an additional set of chromosomes derived from another species; these typically occur after chromosomal doubling and their chromosomal composition would be AABB; if both species have the same number of chromosomes then the derived species would be an allotetraploid

  • Autotetraploids occur from a doubling of the chromosomal composition. This can occur naturally by doubling sometime during the life cycle or artificially through the application of heat, cold or the chemical colchicine. Because an additional set of chromosomes exists, autotetraploids can undergo normal meiosis.

FIGURE 7-6 Contrasting chromosome origins of an autopolyploid versus an allopolyploid karyotype.

FIGURE 7-7 The potential involvement of colchicine() in doubling the chromosome number, as occurs during the production of an autotetraploid. Two pairs of homologous chromosomes are followed. While each chromosome has replicated its DNA earlier during interphase, the chromosomes do not appear as double structures until late prophase. When anaphase fails to occur normally, the chromosome number doubles if the cell reenters interphase.

FIGURE 7-9 The origin and propagation of an amphidiploid().

Species I contains genome A consisting of three distinct chromosomes, a,, a2, and a3.

Species 2 contains genome 6 consisting of two distinct chromosomes, b1 and b2.

Following fertilization between members of the two species and chromosome doubling, a fertile amphidiploid containing two complete diploid genomes (AABB) is formed.

  • Monoploidy

  • An individual that contains one half the normal number of chromosomes is a monoploid and exhibits monoploidy. Monoploids are very rare in nature because recessive lethal mutations become unmasked, and thus they die before they are detected. These alleles normally are not a problem in diploids because their effects are masked by dominant alleles in the genome. Some species such as bees, ants and male bees are normally monoploid because they develop from unfertilized eggs.

  • A stage in the life cycle of some fungal species can also be monoploid.

  • Consequently, these individuals will be sterile.

  • 1/2n

  • Monoploidy has been applied in plant biotechnology to rapidly develop plants from anthers that have a fixed genotype. F1 plants derived from a cross of two parents are grown and anther tissue is used to regenerate new plants using tissue culture techniques.

  • The plants that are derived from this tissue will be monoploid, and the genetics of these individuals can be studied or they can be treated with a chemical to double the chromosome number.

  • What are the advantages of this technique? Theoretically, different recombination products can be fixed much faster than with conventional plant breeding techniques. Plant breeders make crosses and begin selecting in the F2 generation for individuals that show desirable traits. But these selections are then tested in subsequent generations because the lines are not genetically homogeneous or homozygous. Several more generations of testing are normally required before the desired trait is fixed in a line.

  • Using anther culture, though, these recombinants in the F1 gametes are fixed immediately after the chromosomes are doubled (with a drug such as colchicine). They are fixed because after doubling the individual will be homozygous for every gene in the genome. Thus, selection for lines with desirable traits can be accelerated significantly. To date, the limiting factor has been the development of anther culture techniques for different crops. Wheat has been the best success story to date with this technique.


  • One generalization that has been made is that autopolyploids are larger than their diploid counterpart.

  • For example, their flowers and fruits are larger in size which appears to be the result of larger cell size than cell number. This increased size does offer some commercial advantages.


  • 3(autopolyploid)




Genotype Gamete Ratio Phenotypes

AAAa 1AA1Aa all A

AAaa 1AA4Aa1aa 35A1a

Aaaa 1Aa1aa 3A1a





  • a1a2a33

  • a1 + a2 a2 + a3 a1 + a3

  • a3 a1 a2

  • 2nn1/2n-12nn

  • The analysis of plant genomes has provided insight into how these evolutionary events occurred and the rate at which evolution can take place. The three plants genera that will be discussed are Brassica, wheat and Spartina.

  • Important triploid plants include, some potatoes, bananas, watermelons and Winesap apples. All of these crops must be propagated asexually.

  • Examples of tetraploids are alfalfa, coffee, peanuts and McIntosh apples. These also are larger and grow more vigorously.

  • The chromosomal composition of allopolyploids is derived from two different species.

  • The classic experiment that initiated research in allopolyploids was performed by G. Karpechenko in 1928.

  • He knew that cabbage and radish both had a diploid number of 18 chromosomes, and he surmised that if he crossed these two species he should be able to derive offspring with 18 chromosomes.

  • His applied goal was to develop a new plant that contained radish roots and cabbage heads.

  • To his disappointment all of the progeny from the cross appeared to be sterile.

  • It is suggested ,incorrect pairing or no synapsis

  • Surprisingly, though, one day he noticed that some seeds did appear.

  • These were grown, and chromosomal analysis revealed that their diploid number was 36.

  • Apparently, chromosomal doubling had occurred. Therefore balanced gametes were generated because each chromosome had a partner with which to pair.

  • 2n=36

  • R9

  • B9

  • This type of situation where a polyploid is formed from the union of complete sets of chromosomes from two species and their subsequent doubling is called amphidiplpoidy and the species is called an amphidiploid.

  • As a side note, Karpechenko's experiment produced plants with cabbage roots and radish tops.

  • Euploidy and Plant Speciation

  • One goal of plant breeding has been to develop allopolyploids that have new traits that are not seen in other species. The one beneficial allopolyploid developed to date is Triticale.

  • This amphidiploid was developed from the pollination of wheat (Triticum, 2n=42) with rye (Secale, 2n=14). The goal of this experiment was to combine the rugged phenotype of rye with the high yielding characteristics of wheat.

  • The final chromosomal composition was 2n=56 chromosomes. Allopolyploidy has now been demonstrated to have been a major genetic event during plant speciation.

  • Wheat Speciation

  • Wheat has played a major role in the development of the world civilization. The domestication of wheat was a major event in world civilization because it allowed humans to change from nomadic hunter gathers to permanent residents of specific locations. The following is the current suggested development of modern bread wheat.

  • Triticum urartu (AA) X Aegilops speltoides (BB) >>Triticum turgidum (AABB) X Triticum tauschii (DD) >> Triticum aestivum (AABBDD)

  • 142842

  • 50-60

  • T tauschii 14

    T searsii 14

    T monocum 14


    T dicocum 28

    T timopheari 28

    T zhukovskyi 42

    T aestivum 42

  • Archaeological evidence has shown that Triticum turgidum (AABB) was being grown in both Mesopatamia (Tigris and Euphrates River Valley) and in the Nile River Valley 10,000 years ago.

  • Because wild T. tauschii is found only in the mountain region of southern Russia, western Iran and northern Iraq

  • it is thought that the hybridization that produced T. aestivum occurred in these region.

  • It has been suggested that this occurred as recently as 8,000 years ago which coincides with the development of collective settlements by man.

  • The wheats that were developed by the above hybridization scheme are each cultivated today. Cultivated T. turgidum is called durum wheat. North Dakota is essentially the only state in the US that grows durum wheat. This wheat is processed and used for pasta.

  • To describe these species it is necessary to introduce the final symbol X.

  • X is the base number of chromosomes for a specific series of species. For wheat 2n=14 and the base number of chromosomes (X) is 7. So for diploid wheat 2n=2X=14. For the series though, the tetraploid species are 2n=4X=28 chromosomes, the pentaploid are 2n=5X=35 chromosomes and the hexaploid is 2n=6X=42 chromosomes.

  • Brassica Speciation

  • Three Brassica species form a triad from which three other species in the same genera were derived.

  • B. oleracea (broccoli and cauliflower) has a haploid chromosome number of n=9 and

  • the haploid number for B. campesteris (turnip) is n=10.

  • Another Brassica species, B. napus has a haploid number of n=19. This species appears have to been derived by the hybridization of B. oleracea with B. campesteris followed by a doubling of the chromosomes to produce the new species.

Spartinia Speciation

  • The last allopolyploid example is the recent development of a new saltmarsh grass species. In the early nineteenth century seed of American saltmarsh grass (Spartinia alterniflora) was accidentally transported to the southern coast of England and the northern coast of France. The grass began growing in the same location that European saltmarsh grass (S. maritima) was grown. Soon a new species of saltmarsh grass appeared called Townsend's grass (S. townsendii).

  • The growth pattern of this species was more vigorous and soon it had crowded out the other two native species.

  • These characteristics were recognized and soon it was introduced into Holland to stabilize the dikes and subsequently into other locations for the same reason.

  • Chromosomal analysis suggested that Townsend's grass was an amphidiploid because its chromosomal number, 2n=122, could be derived from the American (2n=62) and European (2n=60) chromosome numbers. Apparently a hybridization occurred on the beaches followed by a chromosomal doubling to produce the current species. An important point to consider is how quickly speciation can occur from allopolyploid.

  • Clearly, the Townsend's grass species appeared and became established within 100 years because of its vigorous growth.

  • It has been estimated that about 50% of all angiosperm (flowering plants) are polyploid. The following are some examples of common cultivated plants that are autopolyploids.

  • Wild Species and Cultivated Species

    Wild potato (2n=24)Cultivated Potato (2n=48)

    Wild Cotton (2n=26)Cultivated Cotton (2n=52)

    Dahlia (2n=32)Garden Dahlia (2n=64)

    Wild Tobacco (2n=24)Cultivated Tobacco (2n=48)

    For some plant species a series of successive ploidy levels are seen.


The New World cotton species Gossypium hirsutum has a 2n chromosome number of 52. The Old World species G. thurberiand G. herbaceum each have a 2n number of 26. Hybrids between these species show the following chromosome pairing arrangements at meiosis:

  • Fern species exhibit some of the largest chromosome numbers and these are a result of polyploidy. Adder's tongue fern (Ophiglossum) has a base number of 120 chromosomes. The diploid species is 2n=2X=240 chromosomes.

  • One related species has 2n=10X=1200 chromosomes. This demonstrates the high end of the number of chromosomes that are found in eukaryotic species.

  • 7.6 Variation in Chromosome Structure and Arrangement: An Overview

    The second general class of chromosome aberrations includes structural changes that delete, add, or rearrange substantial portions of one or more chromosomes

  • origin of changes in chromosome structure

  • deletions

  • duplications

  • inversions

  • translocations

  • practice questions

  • chromosomal mutations

    • structure

    • number (ploidy)...

  • chromosome structure mutations phenotypes...

    • abnormal gene # or position

    • break points disrupt gene function

  • chromosome properties

    • pairing affinity during meiotic prophase

      • abnormal patterns in rearrangement

    • chromosome breakage

      • changes structure

      • ends highly reactive (normal telomeres not)

    • loss or gain of chromosome pieces

      • genetic imbalance

      • segmental aneuploidy

  • rearrangements can be

    • spontaneous

    • induced

  • maintained & studied in rearrangement heterozygotes... mainly

  • types of changes

  • 2 general processes

    • break / rejoining

      • spontaneous

      • radiation

  • 1



  • 1,

  • 1.

  • 2.

  • 3.

  • 4.

  • types

    • terminal 1 chromosome break

    • interstitial 2 chromosome breaks

7.7 Deletions

Vitality by DELETIONS

  • size

    • intragenic within 1 gene

      • do not revert ( point mutations)

      • can be viable if gene not vital

    • multigenic > 1 gene

      • do not revert

      • usually homozygous lethal

      • sometimes heterozygous lethal

Cell or chromosome behavior DELETIONS

  • appearance in polytene chromosomes

    • deletion loop

Genetic effect by DELETIONS

  • genetic properties

    • homozygous lethal (~ size, genes)

    • do not revert

    • recombination not possible in deleted segment

    • uncovers recessive alleles on homologue

      • pseudodominance

      • deletion mapping...



DELETION mapping

  • deletion mapping ~ corresponds with linkage maps

  • XX

  • 159X25811258141313N82463826436264302643126432fafacet6fa+fa3C72643326437264392642264193C7fa3C7

DELETIONS deletions & human disease

  • cridu-chat syndrome)5(5P-)55p15.25p

  • chronic myelocvtic leukemiaCML Ph9022 DNA 22 61 40

  • Ph11960NowellHungerfordPhiladelPhiaPh1Ph2222q-Ph9t922q34q11

  • 95Ph1Ph1Ph1

  • ,PhCMLt922q34qll922,Ph

  • deletions & human disease

    • cancer



FIGURE 7-11 The origin of duplicated and deficient regions of chromosomes as a result of unequal crossing over. The tetrad on the left is mispaired during synapsis. A single crossover between chromatids 2 and 3 results in deficient and duplicated chromosomal regions (see chromosomes 2 and 3, respectively, on the right).The two chromosomes uninvolved in the crossover event remain normal in their gene sequence and content

  • types of changes

  • 2 general processes

    • break / rejoining

      • spontaneous

      • radiation

    • crossing over

      • illegitimate


  • types (2 chromosome breaks)

    • tandem adjacent, same order

    • reverse adjacent, reverse order


  • size... similar to deletions

    • intragenic within 1 gene

      • do not revert ( point mutations,)

      • can be viable if genetic balance not critical

    • multigenic > 1 gene

      • do not revert (see below)

      • homozygous lethal if genetic balance critical

      • can be heterozygous lethal if balance critical


  • genetic properties

    • homozygous lethal (~ size, genes)

    • do not revert (see below)

    • illegitimate recombination possible

    • can rescue phenotypes associated with deleted

      segments on homologue

    • explanation for evolution of gene families

The Bar Mutation in Drosophila



  • tandem duplications & gene evolution

    • human hemoglobin genes


  • tandem duplications & gene evolution

    • human hemoglobin genes

Gene Redundancy and AmplificationRibosomal RNA Genes

Although many gene products are not needed in every cell of an organism, other gene products are known to be essential components of all cells. For example, ribosomal RNA mustbe present in abundance in order to support protein synthesis. The more metabolically active a cell is, the higher is the demand for this molecule. We might hypothesize that a single copy of the gene encoding rRNA is inadequate in many cells. Studies using the technique of molecular hybridization, which allows the determination of the percentage of the genome coding for specific RNA sequences, show that our hypothesis is correct! Indeed, multiple copies of genes code for rRNA. Such DNA is called rDNA, and the general phenomenon is called gene redundancy.

  • For example, in the common intestinal bacterium Escherichia coli , about 0.4 percent of the haploid genome consists of rDNA. equivalent to 5-10 copies of the gene.

  • In Drosophila melanogaster, 0.3 percent of the haploid genome, 130 copies rDNA.

  • Although the presence of multiple copies of the same gene is not restricted to those coding for rRNA, we focus on them in this section.

  • In some cells, particularly oocytes, even the normal redundancy of rDNA is insufficient to provide adequate amounts of rRNA and ribosomes. Oocytes store abundant nutrients in the ooplasm for use by the embryo during early development. In addition, more ribosomes are included in the oocytes than in any other cell type.

  • By considering how the amphibian Xenopus laevis acquires this abundance of ribosomes, we shall see a second way in which the amount of rRNA is increased. This phenomenon is called gene amplification.

  • The genes that code for rRNA are located in an area of the chromosome known as the nucleolar organizer region (NOR). The NOR is intimately associated with the nucleolus, which is a processing center for ribosome production. Molecular hybridization analysis has shown that each NOR in the frog Xenopus contains the equivalent of 400 redundant gene copies coding for rRNA. Even this number of genes is apparently inadequate to synthesize the vast amount of ribosomes that must accumulate in the amphibian oocyte to support development following fertilization.

The Role of Gene Duplication in Evolution

  • During the study of evolution, it is intriguing to speculate on the possible mechanisms of genetic variation. The origin of unique gene products present in more recently evolved organisms but absent in ancestral forms is a topic of particular interest. In other words, how do "new" genes arise?In 1970, Susumo Ohno published a provocative monograph, Evolution by Gene Duplication, in which he suggested that gene duplication is essential to the origin of new genes during evolution. Ohno's thesis is based on the supposition that the gene products of unique genes, present as only a single copy in the genome, are indispensable to the survival of members of any species during evolution. Therefore, unique genes are not free to accumulate mutations sufficient to alter their primary function and give rise to new genes.

7.9 Inversions

  • types (2 chromosome breaks)

    • paracentric does not include centromere

    • pericentric does include centromere


  • types (2 chromosome breaks)

    • pericentric does include centromere



(inversion homozygote)

(inversion heterozygote)

(paracentric inversion)

(pericentric inversion)


  • genetic properties

    • no change in total genetic material

    • breakpoints can (but not always) disrupt genes

      • no disruption viable homozygotes

      • disruption heterozygotes only (majority)

    • do not revert

    • recombination in inversion segm. aneuploidy

      • recombinant gametes lethal fertility

      • recombination suppression


  • inversion loops

  • inversion loops


  • crossing over in a pericentric inversion

    • 1 normal viable

    • 1 inversion viable

    • 1 duplication lethal

    • 1 deletion lethal

Consequences Inversions of Inversions During Gamete


  • 1180

  • 180

  • 2

  • (inversion homozygote)

  • (inversion heterozygote)

  • (paracentric inversion)

  • (pericentric inversion)




(inversion loop)





(6 (balanced lethal system)

  • (balanced lethal system)

  • No.3D

  • D/+ x D/+

  • 2/3D/+ : 1/3 +/+ :(1/4DD

  • D/+ x D/++ / + x + / +75%

  • +/+ D/+

  • Muller

  • GlNo.3

D / +

+ /Gl

(permanent hybrid)

D+/++ +Gl/++

++/++ D+/++ D+/+G l ++/+Gl

D+/D+ D+/+Gl +Gl/+Gl

  • No.2




    Cy + Cy +

    + A + A

    Cy + Cy + + A

    Cy + + A + A

  • 1

  • 2

7.10 Translocations

  • reciprocal translocations

    • nonreciprocal translocation

    • Robertsonian translocation (centric fusion) centric fission):

    • can restructure genomes


  • genetic properties

    • no change in total genetic material

    • do not revert

    • meiosis segmental aneuploidy

      • lethality

      • semi-sterility

    • rearrangement of linkage groups

3. translocation)

  • 1

  • 2

  • reciprocal translocation)

  • nonreciprocal translocation):(transposition)

  • whole-arm translocation)

  • (Robertsonian translocation):

  • fission1519

  • 3

  • 2O850%4

(alternate segregation)

(adjacent segregation)



  • 23bwe

  • 23bw/+ e/+bw/bw e/e



  • BurkittB88q24ter)14lq32ter14q+ 8q-t814q24q32)1522

  • Burkitt 3 t8;1480902t(8;22)q24 q11t28p11q24155

  • 8q24cmyc14q32IgH

  • t814Burkitt 8 14q14q88cmyc14IgHcmyc

variegated type of position effect

  • position effect

  • Xw+/ww+44X

  • w+4w+15-23

  • McClintock


    Activator-Dis sociation system



  • in heterozygotes

    • adjacent-1

      2 lethal

    • adjacent-2


      2 lethal

    • alternate

      1 normal

      1 carrier


  • in heterozygotes

    • consider




  • rearrangement of linkage groups

    • T heterozygote a/; a+b+/b x tester a/a; b/b

Translocations in Humans:Familial Down Syndrome

  • Research conducted since 1959 has revealed numerous translocations in members of the human population.

  • One common type of translocation involves breaks at the extreme ends of the short arms of two nonhomologous acrocentric chromosomes.

  • These small segments are lost, and the larger segments fuse at their centromeric region. This type of translocation produces a new, large submetacentric or metacentric chromosome, often called a Robertsonian translocation.

  • One such translocation accounts for cases in which Down syndrome is inherited or familial. Earlier in this chapter we pointed out that most instances of Down syndrome are due to trisomy 21.

  • This chromosome composition results from nondisjunction during meiosis in one parent. Trisomy accounts for over 95 percent of all cases of Down syndrome. In such instances, the chance of the same parents producinga second afflicted child is extremely low.

  • However, in the remaining families with a Down child, the syndrome occurs in a much higher frequency over several generations.

  • Cytogenetic studies of the parents and their offspring from these unusual cases explain the cause of familial Down syndrome.

  • Analysis reveals that one of the parents contains a 14/21 D/G translocation (Figure 7-16). That is, one parent has the majority of the G-group chromosome 21 translocated to one end of the D-group chromosome 14. This individual is phenotypically normal even though he or she has only 45 chromosomes.

  • During meiosis, one-fourth of the individual's gametes have two copies of chromosome 21: a normal chromosome and a second copy translocated to chromosome 14. When such a gamete is fertilized by a standard haploid gamete, the resulting zygote has 46 chromosomes but three copies of chromosome 21. These individuals exhibit Down syndrome. Other potential surviving offspring contain either the standard diploid genome (without a translocation) or the balanced translocation like the parent. Both cases result in normal individuals. Knowledge of translocations has allowed geneticists to resolve the seeming paradox of an inherited trisomic phenotype in an individual with an apparent diploid number of chromosomes.

7.11 Fragile Sites in Humans

  • Ending this chapter with a brief discussion of the results of an intriguing discovery made around 1970 during observations of metaphase chromosomes prepared following human cell culture.

  • In certain individuals, a specific area along one of the chromosomes failed to stain, giving the appearance of a gap. In other individuals whose chromosomes displayed such morphology, the gaps appeared at other positions within the set of chromosomes.

  • Such areas eventually became known as fragile sites, since they appeared to be susceptible to chromosome breakage when cultured in the absence of certain chemicals such as folic acid, B, which is normally present in the culture medium.

  • Fragile sites were at first considered curiosities, until a strong association was subsequently shown to exist between one of the sites and a form of mental retardation.The cause of the fragility at these sites is unknown. Because they represent points susceptible to breakage, these sites may indicate regions where the chromatin is not tightly coiled.

  • Note that even though almost all studies of fragile sites have been carried out in vitro using mitotically dividing cells, clear associations have been established between several of these sites and the corresponding altered phenotype, including mental retardation and cancer

Fragile X Syndrome (Martin-Bell Syndrome

  • Most fragile sites do not appear to be associated with any clinical syndrome. However, individuals bearing a fragile-sensitive site on the X chromosome (Figure 7-17) exhibit the fragile X syndrome (or Martin-Bell syndrome), the most common form of inherited mental retardation.

  • This syndrome affects about 1 in 1250 males and 1 in 2500 females. Because it is a dominant trait, females carrying only one fragile X chromosome can be mentally retarded. Fortunately, the trait is not fully expressed, as only about 30 percent of fragile X females are retarded, whereas about 80 percent of fragile X males are mentally retarded.

  • In addition to mental retardation, affected males have characteristic long, narrow faces with protruding chins, enlarged ears, and increased testicular size. A gene that spans the fragile site may be responsible for this syndrome.

  • This gene, known as FMR-1, is one of a growing number of genes that have been discovered in which a sequence of three nucleotides is repeated many times, expanding the size of the gene. This phenomenon, called trinucleotide repeats, is also recognized in other human disorders, including Huntington disease.

  • In FMR-1, the trinucleotide sequence CGG is repeated in an untranslated area adjacent to the coding sequence of the gene (called the "upstream" region). The number of repeats varies immensely within the human population, and a high number correlates directly with expression of fragile X syndrome.

  • Normal 6 and 54 repeats,

  • Those with 55-200 repeats are considered "carriers" of the disorder. Above 200 repeats leads to expression of the syndrome.It is thought that when the number of repeats reaches this level, the CGG regions of the gene become chemically modified so that the bases within and around the repeat are methylated, causing inactivation of the gene. The normal product of the gene is an RNA-binding protein known to be expressed in the brain. However, the relationship between the absence of this protein and fragile X syndrome is not yet clear..

  • From a genetic standpoint, perhaps the most interesting aspect of fragile X syndrome is the instability of the CGG repeats. An individual with 6-54 repeats transmits a gene containing the same number to his or her offspring. However, those with 55-200 repeats, while not at risk to develop the syndrome, may transmit to their offspring a gene with an increased number of repeats. The number of repeats continues to increase in future generations, demonstrating the phenomenon known as genetic anticipation, first introduced in Chapter 4. Once the threshold of 200 is exceeded, expression of the malady becomes more severe in each successive generation as the number of trinucleotide repeats increases.

  • While the mechanism that leads to the trinucleotide expansion has not yet been established, several factors are known that influence the instability. Most significant is the observation that expansion from the carrier status (55-200 repeats) to the syndrome status (over 200 repeats) occurs during the transmission of the gene by the maternal parent, but not by the paternal parent. Furthermore, several reports suggest that male offspring are more likely to receive the increased repeat size leading to the syndrome than are female offspring. Obviously, we have much to learn about the genetic basis of instability and expansion of DNA sequences

Fragile Sites and Cancer

  • A second link between a fragile site and a human disorder was reported in 1996 by Carlo Croce, Kay Huebner, and their colleagues, who demonstrated an association between an autosomal fragile site and cancer.

  • They showed that the gene FHIT (standing for fragile histidine triad), located within a well-defined fragile site on chromosome 3, is often altered in cells taken from tumors of individuals with lung cancer.

  • A variety of mutations were found in cells derived from the tumors where the DNA had apparently been broken and incorrectly refused, resulting in deletions within the gene. In most cases, these mutations caused the FHIT gene to become inactivated.

  • This gene is part of the fragile region of the autosome designated FRA3B, which has been linked to other cancers, including the esophagus, colon, and stomach. The nature of the genetic alterations found in cancer cells suggests that the FHIT gene, because it is within a fragile region, may be highly susceptible to induced breaks in DNA.

  • If these breaks areincorrectly repaired, cancer-specific chromosome alterations may occur. Thus, this region of the chromosome appears to be particularly sensitive to carcinogen-induced damage, creating a susceptibility to cancer.

  • It will be important to determine experimentally whether molecular polymorphism exists at this and other fragile sites within the human population, causing some individuals to be more susceptible to the effects of carcinogens than others.

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